A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal...

Area of Science:

• Oncology
• Immunotherapy
• Virology

Background:

• Toca 511, a retroviral replicating vector, combined with 5-fluorocytosine (5-FC) converts tumors into 5-fluorouracil (5-FU) factories.
• This strategy has shown promise in brain tumor models, inducing systemic immunity and long-term survival.
• Previous studies demonstrated efficacy in glioma patients, with durable responses observed.

Purpose of the Study:

• To evaluate the efficacy of Toca 511 and 5-FC in metastatic colorectal carcinoma (mCRC) models.
• To assess the impact of this therapy on tumor growth, survival, and immune responses in mCRC.
• To investigate the effect of 5-FC on myeloid-derived suppressor cells (MDSCs) within mCRC tumors.

Main Methods:

• Intravenous (i.v.) administration of Toca 511 followed by 5-FC in two mCRC models.
• Monitoring tumor response, survival rates, and immune memory following treatment.
• Quantifying changes in MDSC populations within liver and brain metastases.

Main Results:

• Toca 511 demonstrated selective uptake in mCRC metastatic lesions.
• Treatment with 5-FC led to significant tumor shrinkage and improved survival.
• Therapy induced immune memory and a notable reduction in tumor-infiltrating MDSCs.

Conclusions:

• Toca 511 and 5-FC represent a promising immunotherapeutic strategy for mCRC.
• The observed reduction in MDSCs suggests a mechanism for enhanced anti-tumor immunity.
• Further clinical investigation in solid tumors, including mCRC, is warranted and ongoing.